title: Insulin resistance protects the heart from fuel overload in dysregulated metabolic states.
abstract: Reversing impaired insulin sensitivity has been suggested as treatment for heart failure. However, recent clinical evidence suggests the opposite. Here we present a line of reasoning in support of the hypothesis that insulin resistance protects the heart from the consequences of fuel overload in the dysregulated metabolic state of obesity and diabetes. We discuss pathways of myocardial fuel toxicity, as well as several layers of defense against fuel overload. Our reassessment of the literature suggests that in the heart, insulin-sensitizing agents result in an elimination of some of the defenses, leading to cytotoxic damage. In contrast, a normalization of fuel supply should either prevent or reverse the process. Taken together, we offer a new perspective on insulin resistance of the heart.
authors.affiliation: Division of Cardiology, Department of Internal Medicine, The University of Texas School of Medicine at Houston, Houston, Texas;
authors.forename: Heinrich
authors.initials: H
authors.lastname: Taegtmeyer
authors.forename: Christophe
authors.initials: C
authors.lastname: Beauloye
authors.forename: Romain
authors.initials: R
authors.lastname: Harmancey
authors.forename: Louis
authors.initials: L
authors.lastname: Hue
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism*
chemical_list: D007328:Insulin
keywords: insulin resistance; metabolism; obesity